Antiviral Effect, Safety, and Pharmacokinetics of BI201335 +PegIFN/RBV in HCV-GT1 (SILEN-C1&2)

Boehringer Ingelheim719 enrolled

Overview

The objective was to investigate the antiviral effect, safety, and pharmacokinetics of BI 201335 (Faldaprevir), given as a soft gelatine capsule, in patients with hepatitis C virus (HCV) genotype 1 infection. Combination therapy of BI 201335 (Faldaprevir) with pegylated interferon α-2a (PegIFN) and ribavirin (RBV), with or without a 3-day lead-in, was assessed in treatment-naïve (TN) and treatment experienced (TE) patients.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

719

Conditions

Hepatitis C, Chronic

Interventions

BI 201335 NA 240 mg QD / LIDRUG

240mg BI 201335 NA (Faldaprevir) once daily with a 3 days lead-in phase of PegIFN/RB, 24 weeks

PegIFN/RBVDRUG

PegIFN (180 µg/wk) and RBV (1000/1200mg/d), 24 or 48 weeks

BI 201335 NA 120mg QD / LIDRUG

120mg BI 201335 NA (Faldaprevir) once daily, for 24 weeks

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion criteria: chronic HCV GT1; therapy-naive to IFN, PegIFN, or RBV; HCV VL \>=100,000 IU/mL Liver biopsy within 2 years prior to study enrolment showing necroinflammatory activity or presence of fibrosis Normal retinal finding on fundoscopy within 6 months prior to Day 1 age 18-65 years Females and males with adequate contraception Exclusion criteria: Mixed genotype (1/2, 1/3, or 1/4), diagnosed by genotypic testing at screening Previous treatment with protease inhibitor Evidence of liver disease due to causes other than chronic HCV infection HIV-1 or HIV-2 positive HBV positive Decompensated liver disease, or history of decompensated liver disease Active or suspected malignancy or history of malignancy within the last 5 years History of alcohol or drug abuse within the past 12 months. Usage of any investigational drug within 30 days prior to enrolment, or 5 half-lives, whichever is longer Known hypersensitivity to any ingredient of the study drugs Condition that is defined as one which in the opinion of the investigator may put the patient at risk because of participation in the study or may influence the results of the study or the patient's ability to participate in the study Alpha-fetoprotein value \> 100ng/mL at screening; if \>20ng/mL and \<=100ng/mL, patients can be included if there is no evidence of liver cancer in two congruent imaging studies Total bilirubin \> 1.5x ULN wiht ratio of direct/indirect \>1. ALT or AST levels \> 5x ULN INR prolonged to \>1.5x ULN Exclusion criteria related to PegIFN and/or RBV restrictions.

Locations (100)

Outcomes

Primary Outcomes

Virological Response 4 Weeks After the End of Treatment With BI 201335 or Placebo

An achieved virological response is defined as the plasma Hepatitis C Virus RiboNucleic Acid (HCV RNA) level below the lower limit of detection (BLD). This data was only collected for patients, who stopped trial participation at Week 24 and did not continue with PegIFN/RBV until Week 48. The lower limit of quantification (BLQ) of this assay was 25 IU/mL and the lower limit of detection (BLD) was 10 IU/mL at the time of the protocol finalisation. During the course of the trial, the manufacturer defined BLD as '\< 25 IU/mL, not detectable' and BLQ as '\< 25 IU/mL, detectable'.

Time frame: Week 28

Sustained Virological Response 24 Weeks (SVR24) After Completion of All Therapy

Virological (VL) response was defined as the plasma HCV RNA level below the lower limit of detection. The first VL measurement that occurred in the time window ≥ Day 155 (from End Of Treatment on) was selected for the determination of SVR24. Therefore, patients with virological load BLD 24 weeks after completion of therapy, who had a rebound after this time point (outside the defined time window of 155 days after end of all treatments) were identified as SVR24 achieved.

Time frame: Day 155 after the end of all treatment

Secondary Outcomes

Virological Response at Week 2

Viral load (plasma HCV RNA level) below the lower limit of quantification at Week 2 (\< 25 IU/ml, detectable or undetectable)

Time frame: Week 2

Virological Response at Week 4

Viral load (plasma HCV RNA level) below the lower limit of quantification at Week 4 (\< 25 IU/ml, detectable or undetectable)

Time frame: Week 4

Early Virological Response (EVR)

Early Virological Response (EVR) is defined as ≥ 2 log 10 reduction in plasma HCV RNA level from baseline at Week 12

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

PegIFN (180 µg/wk) and RBV (1000/1200mg/d),48 weeks

BI 201335 NA 240 mg QDDRUG

240mg BI 201335 NA (Faldaprevir) once daily, 24 weeks

PegIFN/RBVDRUG

PegIFN (180 µg/wk) and RBV (1000/1200mg/d),48 weeks

BI 201335 NA 240 mg QDDRUG

240mg BI 201335 NA (Faldaprevir) once daily, 24 weeks

PegIFN/RBVDRUG

PegIFN (180 µg/wk) and RBV (1000/1200mg/d), 24 or 48 weeks

BI 201335 NA 240 mg BIDDRUG

240mg BI 201335 NA (Faldaprevir) twice, 24 weeks

PegIFN/RBVDRUG

PegIFN (180 µg/wk) and RBV (1000/1200mg/d),48 weeks

PegIFN/RBVDRUG

PegIFN (180 µg/wk) and RBV (1000/1200mg/d),48 weeks

BI 201335 NA 240 mg QDDRUG

240mg BI 201335 NA (Faldaprevir) once daily, 24 weeks

PegIFN/RBVDRUG

PegIFN (180 µg/wk) and RBV (1000/1200mg/d), 24 or 48 weeks

1220.5.0001 Boehringer Ingelheim Investigational Site

San Francisco, California, United States

1220.5.0008 Boehringer Ingelheim Investigational Site

San Francisco, California, United States

1220.5.0005 Boehringer Ingelheim Investigational Site

Chicago, Illinois, United States

1220.5.0006 Boehringer Ingelheim Investigational Site

Lutherville, Maryland, United States

1220.5.0002 Boehringer Ingelheim Investigational Site

New York, New York, United States

1220.5.0003 Boehringer Ingelheim Investigational Site

New York, New York, United States

1220.5.0007 Boehringer Ingelheim Investigational Site

Philadelphia, Pennsylvania, United States

1220.5.0010 Boehringer Ingelheim Investigational Site

Germantown, Tennessee, United States

1220.5.0009 Boehringer Ingelheim Investigational Site

Nashville, Tennessee, United States

1220.5.0004 Boehringer Ingelheim Investigational Site

Austin, Texas, United States

...and 90 more locations

Time frame: Baseline and Week 12

Extended Rapid Virological Response (eRVR)

Extended Rapid Virological Response (eRVR) is defined as plasma HCV RNA levels below the lower limit of quantification at Week 4 and below the lower limit of detection at Week 12

Time frame: Week 4 and Week 12

Complete Early Virological Response (cEVR)

Complete Early Virological Response (cEVR) is defined as plasma HCV RNA level below the lower limit of detection at Week 12

Time frame: Week 12

End of Treatment Response at Week 24

End of Treatment Response of BI 201335 or placebo (ETR BI 201335/placebo ) is defined as plasma HCV RNA level below the lower limit of detection at Week 24.

Time frame: Week 24

End of Treatment Response at End of All Therapy

End of Treatment Response (ETR) is defined as plasma HCV RNA level below the lower limit of detection at end of all therapy, i.e. at Week 24 or Week 48

Time frame: Week 24 or Week 48

Sustained Virological Response 12 Weeks (SVR12) After Completion of All Therapy

Sustained Virological Response 12 Weeks (SVR12) after completion of all therapy is defined as plasma HCV RNA level below the lower limit of detection at 12 weeks after completion of all therapy, i.e. at Week 36 or 60

Time frame: Week 36 or Week 60

Time to Reach a Plasma HCV RNA Level Below the Lower Limit of Detection

Summary of time (i.e Median number of days) to reach a plasma HCV RNA level below limit of detection (BLD)

Time frame: On or after day 155 post end of all treatment

Time to Loss of Virological Response

Time to loss of virological response, defined as the last value below the lower limit of detection in a patient who subsequently had 2 consecutive plasma HCV RNA level measurements ≥100 IU/mL. Patients that did not achieve suppression of plasma HCV RNA levels below the lower limit of detection until Week 24 were defined as having a time to failure of zero. Time is expressed in Median number of days.

Time frame: Week 24

Virological Rebound

Virological rebound is defined as increase of ≥ 1 log 10 in plasma HCV RNA level from a quantifiable nadir, or to ≥ 250 IU/mL after previous nadir \< 25 IU/mL (detectable), or to ≥ 100 IU/mL after a previous viral load below the lower limit of detection. Note that this is numerical rebound, not requiring confirmation with a re-measurement.

Time frame: Week 24 or Week 48

Breakthrough on BI 201335/Placebo (Rebound While All 3 Treatments Were Still Ongoing)

Number of patients with Unconfirmed rebound ( ≥ 1log10 increase in HCV mRNA) while on BI201335/placebo + 5 days washout.

Time frame: Up to Week 24

Breakthrough on PegIFN/RBV (Rebound While Only PegIFN/RBV Treatment Alone Was Still Ongoing)

Number of patients with Unconfirmed rebound (≥ 1log10 increase in HCV mRNA) while on PegIFN/RBV treatment + 5 days washout.

Time frame: Week 24 through Week 48

Relapse

Relapse was rebound after the viral load at end of all treatment had been below the lower limit of detection, or, if the value at end of all treatment was missing, after both the last value before End of Treatment (EOT) and the first value after End of Treatment were below the lower limit of detection. Patients could experience relapse at any point post-treatment.

Time frame: post-End of treatment (i.e. post 48 weeks)

Change From Baseline to Week 24 in Diastolic Blood Pressure and Systolic Blood Pressure

Baseline is defined as the last value before the initial drug administration of BI 201335 or placebo.